This proposal addresses several important issues relating to human health and disease states. Lipid peroxidation has been implicated in neoplastic transformations, oxygen toxicity, and the formation of age pigments. The modification of membrane and protein structure are also suggested to result from the destructive effects of free radicals. Because of this interest in oxygen and radical toxicity, the mechanism of lipid peroxidation has been the focus of much attention, but there are still important aspects of this problem that are unsolved. This proposal addresses several questions relating to the mechanism of autoxidation of steroids and fatty acids. HPLC/MS will be used extensively in this study because we have shown this technique to be particularly powerful as applied to steroid and oleate peroxidation. A second aspect of free radical chemistry that this proposal addresses is the control of stereochemistry in free radical reactions. We have evidence suggesting that the general problem of stereochemical control in radical C=C addition reactions can be solved by using amide auxiliaries on the target alkene carbon and on the radical center undergoing addition. The discovery of significant stereochemical control in radical addition leads to consideration of iterative free radical processes, such as oligomerizations, for construction of compounds with multiple stereocenters in one reaction sequence. Template radical macrocyclization is also proposed using steroid templates for constructing oligomers of well defined length. A third problem that this proposal addresses is the design and use of photoreversible serine protease inhibitors. These may well provide a valuable research tool in studying enzyme mechanisms by serving to cage the enzyme activity until a photon releases the active site for catalysis. Our strategy may also provide a novel way to control the important blood coagulation cascade. We will also address the important question of how molecular aggregates such as micelles and lipid bilayers may influence organic reactivity. This problem will be approached at the fundamental level via the design synthesis of optically pure tripod surfactant molecules. Chiral recognition and substrate-template reactions in molecular aggregates will also be investigated with these tripod molecules.